3u8l: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of the acetylcholine binding protein (AChBP) from Lymnaea stagnalis in complex with NS3570 (1-(5-phenylpyridin-3-yl)-1,4-diazepane)== | |||
<StructureSection load='3u8l' size='340' side='right' caption='[[3u8l]], [[Resolution|resolution]] 2.32Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3u8l]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Lymnaea_stagnalis Lymnaea stagnalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U8L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U8L FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=09Q:1-(5-PHENYLPYRIDIN-3-YL)-1,4-DIAZEPANE'>09Q</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3u8j|3u8j]], [[3u8k|3u8k]], [[3u8m|3u8m]], [[3u8n|3u8n]], [[1uw6|1uw6]], [[1uv6|1uv6]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3u8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u8l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3u8l RCSB], [http://www.ebi.ac.uk/pdbsum/3u8l PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The alpha4beta2 subtype of the nicotinic acetylcholine receptor has been pursued as a drug target for treatment of psychiatric and neurodegenerative disorders and smoking cessation aids for decades. Still, a thorough understanding of structure-function relationships of alpha4beta2 agonists is lacking. Using binding experiments, electrophysiology and x-ray crystallography we have investigated a consecutive series of five prototypical pyridine-containing agonists derived from 1-(pyridin-3-yl)-1,4-diazepane. A correlation between binding affinities at alpha4beta2 and the acetylcholine-binding protein from Lymnaea stagnalis (Ls-AChBP) confirms Ls-AChBP as structural surrogate for alpha4beta2 receptors. Crystal structures of five agonists with efficacies at alpha4beta2 from 21-76% were determined in complex with Ls-AChBP. No variation in closure of loop C is observed despite large efficacy variations. Instead, the efficacy of a compound appears tightly coupled to its ability to form a strong intersubunit bridge linking the primary and complementary binding interfaces. For the tested agonists, a specific halogen bond was observed to play a large role in establishing such strong intersubunit anchoring. | |||
Intersubunit bridge formation governs agonist efficacy at nicotinic acetylcholine alpha4beta2 receptors: unique role of halogen bonding revealed.,Rohde LA, Ahring PK, Jensen ML, Nielsen EO, Peters D, Helgstrand C, Krintel C, Harpsoe K, Gajhede M, Kastrup JS, Balle T J Biol Chem. 2012 Feb 3;287(6):4248-59. Epub 2011 Dec 13. PMID:22170047<ref>PMID:22170047</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[Acetylcholine binding protein|Acetylcholine binding protein]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Lymnaea stagnalis]] | [[Category: Lymnaea stagnalis]] | ||
[[Category: Ahring, P K | [[Category: Ahring, P K]] | ||
[[Category: Balle, T | [[Category: Balle, T]] | ||
[[Category: Gajhede, M | [[Category: Gajhede, M]] | ||
[[Category: Harpsoe, K | [[Category: Harpsoe, K]] | ||
[[Category: Helgstrand, C | [[Category: Helgstrand, C]] | ||
[[Category: Jensen, M L | [[Category: Jensen, M L]] | ||
[[Category: Kastrup, J S | [[Category: Kastrup, J S]] | ||
[[Category: Krintel, C | [[Category: Krintel, C]] | ||
[[Category: Nielsen, E O | [[Category: Nielsen, E O]] | ||
[[Category: Peters, D | [[Category: Peters, D]] | ||
[[Category: Rohde, L A.H | [[Category: Rohde, L A.H]] | ||
[[Category: Acetylcholine]] | [[Category: Acetylcholine]] | ||
[[Category: Acetylcholine-binding protein]] | [[Category: Acetylcholine-binding protein]] | ||
Revision as of 06:50, 21 December 2014
Crystal structure of the acetylcholine binding protein (AChBP) from Lymnaea stagnalis in complex with NS3570 (1-(5-phenylpyridin-3-yl)-1,4-diazepane)
| ||||||||||||
